Noncovalently particle-anchored cytokines with prolonged tumor retention safely elicit potent antitumor immunity.

Preclinical studies have shown that immunostimulatory cytokines elicit antitumor immune responses but their clinical use is limited by severe immune-related adverse events upon systemic administration. Here, we report a facile and versatile strategy for noncovalently anchoring potent Fc-fused cytokine molecules to the surface of size-discrete particles decorated with Fc-binding peptide for local administration. Following intratumoral injection, particle-anchored Fc cytokines exhibit size-dependent intratumoral retention. The 1-micrometer particle prolongs intratumoral retention of Fc cytokine for over a week and has minimal systemic exposure, thereby eliciting antitumor immunity while eliminating systemic toxicity caused by circulating cytokines. In addition, the combination of these particle-anchored cytokines with immune checkpoint blockade antibodies safely promotes tumor regression in various syngeneic tumor models and genetically engineered murine tumor models and elicits systemic antitumor immunity against tumor rechallenge. Our formulation strategy renders a safe and tumor-agnostic approach that uncouples cytokines' immunostimulatory properties from their systemic toxicities for potential clinical application.

Recent advances in enantioselective ring-opening polymerization and copolymerization.

Precisely controlling macromolecular stereochemistry and sequences is a powerful strategy for manipulating polymer properties. Controlled synthetic routes to prepare degradable polyester, polycarbonate, and polyether are of recent interest due to the need for sustainable materials as alternatives to petrochemical-based polyolefins. Enantioselective ring-opening polymerization and ring-opening copolymerization of racemic monomers offer access to stereoregular polymers, specifically enantiopure polymers that form stereocomplexes with improved physicochemical and mechanical properties. Here, we highlight the state-of-the-art of this polymerization chemistry that can produce microstructure-defined polymers. In particular, the structures and performances of various homogeneous enantioselective catalysts are presented. Trends and future challenges of such chemistry are discussed.

Implantable optical fibers for immunotherapeutics delivery and tumor impedance measurement.

Immune checkpoint blockade antibodies have promising clinical applications but suffer from disadvantages such as severe toxicities and moderate patient-response rates. None of the current delivery strategies, including local administration aiming to avoid systemic toxicities, can sustainably supply drugs over the course of weeks; adjustment of drug dose, either to lower systemic toxicities or to augment therapeutic response, is not possible. Herein, we develop an implantable miniaturized device using electrode-embedded optical fibers with both local delivery and measurement capabilities over the course of a few weeks. The combination of local immune checkpoint blockade antibodies delivery via this device with photodynamic therapy elicits a sustained anti-tumor immunity in multiple tumor models. Our device uses tumor impedance measurement for timely presentation of treatment outcomes, and allows modifications to the delivered drugs and their concentrations, rendering this device potentially useful for on-demand delivery of potent immunotherapeutics without exacerbating toxicities.